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2.
Sci Rep ; 14(1): 21639, 2024 09 16.
Article in English | MEDLINE | ID: mdl-39284844

ABSTRACT

Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.


Subject(s)
Capsicum , Food Handling , Capsicum/chemistry , Food Handling/methods , Fatty Acids/analysis , Phenols/analysis , Desiccation/methods , Taste , Nutritive Value , Capsaicin/analysis
4.
J Med Chem ; 67(18): 16002-16017, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39287926

ABSTRACT

RNA molecules, similar to proteins, fold into complex structures to confer diverse functions in cells. The intertwining of functions with RNA structures offers a new therapeutic opportunity for small molecules to bind and manipulate disease-relevant RNA pathways, thus creating a therapeutic realm of RNA-binding small molecules. The ongoing interest in RNA targeting and subsequent screening campaigns have led to the identification of numerous compounds that can regulate RNAs from splicing, degradation to malfunctions, with therapeutic benefits for a variety of diseases. Moreover, along with the rise of RNA-based therapeutics, RNA-binding small molecules have expanded their application to the modification, regulation, and delivery of RNA drugs, leading to the burgeoning interest in this field. This Perspective overviews the emerging roles of RNA-binding small molecules in drug discovery and delivery, covering aspects from their action fundamentals to therapeutic applications, which may inspire researchers to advance the field.


Subject(s)
Drug Discovery , RNA , Small Molecule Libraries , Humans , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Small Molecule Libraries/metabolism , RNA/metabolism , RNA/chemistry , Drug Delivery Systems , Animals
5.
BMJ Open ; 14(9): e078526, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39289018

ABSTRACT

INTRODUCTION: Stroke is a common cause of death and disability in the older adult and increases the risk and severity of cognitive impairment, which is a factor for long-term death among stroke survivors. Some studies have focused on the effects of reminiscence therapy with different media on stroke survivors. It is currently unclear which is the best medium. This protocol aims to deal with this problem by using a network meta-analysis. METHODS AND ANALYSIS: Published randomised controlled trials will be included if reminiscence therapy plus usual care was applied in older adult patients who had a stroke in the experimental group and usual care was applied in the control group. Six electronic databases will be searched from their inception to August 2023, including the Cochrane Library, CINAHL, PubMed, Web of Science, Medline and Embase. The media of reminiscence therapy may include (but not restricted to) old photos, music or movies. Outcomes will be cognitive function and negative moods. Study selection, data extraction and quality assessment will be performed independently by two reviewers. The risk of bias (RoB) of the included studies will be evaluated in accordance with the Cochrane Collaboration's RoB tool. The evidence quality will be measured based on the Grading of Recommendations Assessment, Development and Evaluation. To compare the efficacy of reminiscence therapy with different media, standard pairwise meta-analysis and Bayesian network meta-analysis will be conducted. The probabilities of intervention for all outcomes will be ranked based on the surface under the cumulative ranking curve. ETHICS AND DISSEMINATION: Ethical approval is not required for reviewing published studies. The findings will be submitted to a peer-reviewed journal for review and publication to provide important evidence for clinicians and guideline developers to determine interventions for older adult patients who had a stroke. PROSPERO REGISTRATION NUMBER: CRD42023447828.


Subject(s)
Cognition , Network Meta-Analysis , Stroke , Humans , Aged , Stroke/therapy , Stroke/complications , Systematic Reviews as Topic , Affect , Stroke Rehabilitation/methods , Randomized Controlled Trials as Topic , Mental Recall , Cognitive Dysfunction/therapy , Research Design
6.
Luminescence ; 39(9): e4885, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39238366

ABSTRACT

Near-infrared (NIR) fluorescent probes with aggregation-induced emission (AIE) properties are of great significance in cell imaging and cancer therapy. However, the complexity of its synthesis, poor photostabilities, and expensive raw materials still pose some obstacles to their practical application. This study reported an AIE luminescent material with red emission and its application in in vitro imaging and photodynamic therapy (PDT) study. This material has the characteristics of simple synthesis, large Stokes shift, good photostabilities, and excellent lipid droplets-specific testing ability. Interestingly, this red-emitting material can effectively produce reactive oxygen species (ROS) under white light irradiation, further achieving PDT-mediated killing of cancer cells. In conclusion, this study demonstrates a simple approach to synthesize NIR AIE probes with both imaging and therapeutic effects, providing an ideal architecture for constructing long-wavelength emission AIE materials.


Subject(s)
Fluorescent Dyes , Infrared Rays , Lipid Droplets , Photochemotherapy , Reactive Oxygen Species , Humans , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/pharmacology , Lipid Droplets/chemistry , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/analysis , Reactive Oxygen Species/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Cell Survival/drug effects , Optical Imaging , Molecular Structure , HeLa Cells
7.
Diabetes Obes Metab ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39228266

ABSTRACT

OBJECTIVE: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes. METHODS: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). RESULTS: In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-ß) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: ß: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (ß: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose. CONCLUSIONS: Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.

8.
Article in English | MEDLINE | ID: mdl-39243141

ABSTRACT

In eukaryotic cells, gene expression begins with transcription in the nucleus, followed by the maturation of messenger RNAs (mRNAs). These mRNA molecules are then exported to the cytoplasm through the nuclear pore complex (NPC), a process that serves as a critical regulatory phase of gene expression. The export of mRNA is intricately linked to precursor mRNA (pre-mRNA) processing, ensuring that only properly processed mRNA reaches the cytoplasm. This coordination is essential, as recent studies have revealed that mRNA export factors not only assist in transport but also influence upstream processing steps, adding a layer of complexity to gene regulation. Furthermore, the export process competes with RNA processing and degradation pathways, maintaining a delicate balance vital for accurate gene expression. While these mechanisms are generally conserved across eukaryotes, significant differences exist between yeast and higher eukaryotic cells, particularly due to the more genome complexity of the latter. This review delves into the current research on mRNA export in higher eukaryotic cells, focusing on its role in the broader context of gene expression regulation and highlighting how it interacts with other gene expression processes to ensure precise and efficient gene functionality in complex organisms.

9.
Asian J Psychiatr ; 101: 104205, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39243662

ABSTRACT

Mental disorders are becoming increasingly prevalent worldwide, and accurate incidence forecasting is crucial for effective mental health strategies. This study developed a long short-term memory (LSTM)-based recurrent neural network model to predict schizophrenia in inpatients in Taiwan. Data was collected on individuals aged over 20 years and diagnosed with schizophrenia between 1998 and 2015 from the National Health Insurance Research Database (NHIRD). The study compared six models, including LSTM, exponential smoothing, autoregressive integrated moving average, particle swarm optimization (PSO), PSO-based support vector regression, and deep neural network models, in terms of their predictive performance. The results showed that the LSTM model had the best accuracy, with the lowest mean absolute percentage error (2.34), root mean square error (157.42), and mean average error (154,831.70). This finding highlights the reliability of the LSTM model for forecasting mental disorder incidence. The study's findings provide valuable insights that can help government administrators devise clinical strategies for schizophrenia, and policymakers can use these predictions to formulate healthcare education and financial planning initiatives, fostering support networks for patients, caregivers, and the public.

10.
Nat Commun ; 15(1): 7459, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198440

ABSTRACT

Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes.


Subject(s)
Histidine , Protein Processing, Post-Translational , Zinc Fingers , Histidine/metabolism , Methylation , Humans , Epigenome , HEK293 Cells , Methyltransferases/metabolism , Methyltransferases/genetics
11.
Ecotoxicol Environ Saf ; 283: 116837, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39121655

ABSTRACT

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.


Subject(s)
Kidney , Mediation Analysis , Metals, Heavy , Tumor Necrosis Factor-alpha , Tumor Necrosis Factor-alpha/blood , Humans , Male , Female , Kidney/drug effects , Middle Aged , Metals, Heavy/blood , Metals, Heavy/toxicity , Adult , Environmental Pollutants/blood , Environmental Pollutants/toxicity , Environmental Exposure/adverse effects , Linear Models , Arsenic/blood , Arsenic/toxicity , Metals/blood , Metals/toxicity
12.
Ecotoxicol Environ Saf ; 284: 116885, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39151371

ABSTRACT

Air pollution has become a major global threat to human health. Urbanization and industrialization over the past few decades have increased the air pollution. Plausible connections have been made between air pollutants and dementia. This study used machine learning algorithms (k-nearest neighbors, random forest, gradient-boosted decision trees, eXtreme gradient boosting, and CatBoost) to investigate the association between cognitive impairment and air pollution. Data from the Taiwan Biobank and 75 air-pollution-monitoring stations in Taiwan were analyzed to determine individual levels of exposure to air pollutants. The pollutants examined were particulate matter with a diameter of ≤ 2.5 µm (PM2.5), nitrogen dioxide, nitric oxide, carbon monoxide, and ozone. The results revealed that the most strongly correlated with cognitive impairment were ozone, PM2.5, and carbon monoxide levels with adjustment of educational level, age, and household income. The model based on these factors achieved accuracy as high as 0.97 for detecting cognitive impairment, indicating a positive association between air pollutions and cognitive impairment.


Subject(s)
Air Pollutants , Air Pollution , Algorithms , Cognitive Dysfunction , Environmental Monitoring , Machine Learning , Particulate Matter , Taiwan/epidemiology , Air Pollution/adverse effects , Air Pollution/statistics & numerical data , Humans , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/epidemiology , Particulate Matter/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Aged , Ozone/analysis , Nitrogen Dioxide/analysis , Male , Carbon Monoxide/analysis , Female , Middle Aged , Nitric Oxide/analysis , Environmental Exposure
14.
Article in English | MEDLINE | ID: mdl-39093066

ABSTRACT

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

15.
Water Res ; 266: 122337, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39216130

ABSTRACT

Optimizing nitrogen removal is crucial for ensuring the efficient operation of wastewater treatment plants (WWTPs), but it is susceptible to variations in influent conditions and operational parameter constraints, and conflicts with the energy-saving and carbon emission reduction goals. To address these issues, this study proposes a hybrid framework integrating process simulation, machine learning, and multi-objective genetic algorithms for nitrogen removal diagnosis and optimization, aiming to predict the total nitrogen in effluent, diagnose nitrogen over-limit risks, and optimize the control strategies. Taking a full-scale WWTP as a case study, a process time-lag simulation-enhanced machine learning model (PTLS-ML) was developed, achieving R2 values of 0.94 and 0.79 for the training and testing sets, respectively. The proposed model successfully identified the potential reasons of nitrogen over-limit risks under different influent conditions and operational parameters, and accordingly provided optimization suggestions. In addition, the multi-objective optimization (MOO) algorithms analysis further demonstrated that maintaining 4-6 mg/L total nitrogen concentration in effluent by adjusting process operational parameters can effectively balance multiple objectives (i.e., effluent water quality, operating costs, and greenhouse gas emissions), achieving coordinated optimization. This framework can serve as a reference for stable operation, energy-saving, and emission reduction in the nitrogen removal of WWTPs.

16.
Phytochemistry ; 227: 114232, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39097216

ABSTRACT

A bioassay-guided isolation from Atractylodes lancea (Thunb.) DC. obtained 22 compounds, including eight previously undescribed sesquiterpenoids and polyacetylenes (1, 3 and 12-17), as well as fourteen known analogues, and their structures were confirmed by extensive spectroscopic methods. This study evaluated their antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) for the first time, as well as anti-inflammatory activity. Most of them, including new compounds, showed varying degrees of antibacterial activity against S. aureus and MRSA. Notably, compound 21 exhibited significant antibacterial activity against four different bacteria (MIC 6.25-20.00 µg/mL). This suggested that 21 may have the potential to be developed into a broad-spectrum antibacterial agent. Moreover, except for 9 and 11, most compounds exhibited great anti-inflammatory activity (IC50 1.92-37.91 µM), and iNOS might be a potential target of these compounds according to the molecular docking analysis.


Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Atractylodes , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Atractylodes/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Molecular Structure , Molecular Docking Simulation , Animals , Structure-Activity Relationship , Mice , Dose-Response Relationship, Drug , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Biological Assay , RAW 264.7 Cells , Staphylococcus aureus/drug effects
17.
J Hazard Mater ; 478: 135564, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39173392

ABSTRACT

Environmental plastic fragments have been verified as byproducts of large plastic and its secondary pollutants including micro and nanoplastics. There are few quantitative studies available, but their contours have values for the weathering mechanisms. We used geometric descriptors, fractal dimensions, and Fourier descriptors to characterize field and artificial polyethylene and polypropylene samples as a means of investigating the contour characteristics. It provides a methodological framework for contour classification. Unsupervised classification was performed using self-organizing neural networks with size-invariance parameters. We revealed the isometric phenomenon of plastic fragments during fragmentation, i.e., that the degree of contour rounding and complexity increase and decrease, respectively, with decreasing fragment size. With an average error rate of 8.9 %, we can distinguish artificial samples from field samples. It was also validated by the difference in Carbonyl Index between groups. We propose a two-stage process for plastic fragmentation and give three types of contour features which were key in the description of fragmented contours, i.e., size, complexity, and rounding. Our work will improve the accuracy of characterizations regarding the weathering and fragmentation processes of certain kinds of plastic fragments. The contour parameters also have the potential to be applied in more realistic scenarios and varied polymers.

18.
Clin Ther ; 46(9): 702-710, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39112102

ABSTRACT

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.


Subject(s)
Hyperkalemia , Silicates , Humans , Hyperkalemia/drug therapy , Silicates/adverse effects , Silicates/therapeutic use , Silicates/administration & dosage , Male , Female , Middle Aged , Double-Blind Method , China , Aged , Adult , Treatment Outcome , Potassium/blood
19.
Brachytherapy ; 23(5): 617-622, 2024.
Article in English | MEDLINE | ID: mdl-39079841

ABSTRACT

PURPOSE: This study aimed to evaluate the effectiveness and safety of iodine-125 brachytherapy as a treatment for right lower paratracheal lymph node metastasis following unsuccessful prior therapies. METHODS: A retrospective review of patients who underwent iodine-125 brachytherapy for right lower paratracheal lymph node metastasis was conducted. The study included 24 patients who met the predefined criteria. Iodine-125 seeds were implanted under CT guidance, and treatment planning was performed using a treatment planning system. The primary endpoint was the objective response rate (ORR), while overall survival (OS) and complications were secondary endpoints. RESULTS: The ORR was 87.5%, with 4 patients achieving complete response (CR) and 17 patients achieving partial response (PR). The mean diameter of metastatic lymph nodes significantly reduced from 40.21 ± 6.66 mm before treatment to 12.25 ± 9.27 mm at the last follow-up (p < 0.001). The median OS was 14.70 months, with 1-year and 2-year survival rates of 78.9% and 20.9%, respectively. Clinical symptoms significantly improved, as indicated by increased Karnofsky Performance Score (KPS) scores. Complications were manageable, with no procedure-related deaths. CONCLUSION: Iodine-125 brachytherapy demonstrated promising efficacy and safety as an alternative treatment for right lower paratracheal lymph node metastasis after unsuccessful prior therapies.


Subject(s)
Brachytherapy , Iodine Radioisotopes , Lymphatic Metastasis , Palliative Care , Tomography, X-Ray Computed , Humans , Brachytherapy/methods , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Retrospective Studies , Lymphatic Metastasis/radiotherapy , Aged , Female , Palliative Care/methods , Adult , Treatment Failure , Lymph Nodes/pathology , Aged, 80 and over , Treatment Outcome , Radiotherapy, Image-Guided/methods , Survival Rate
20.
Colloids Surf B Biointerfaces ; 242: 114109, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39047644

ABSTRACT

Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond, is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON's large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON's rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro. The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo, showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy.


Subject(s)
Boron Compounds , Glutathione , Immunotherapy , Animals , Boron Compounds/chemistry , Boron Compounds/pharmacology , Mice , Immunotherapy/methods , Glutathione/chemistry , Glutathione/metabolism , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Mice, Inbred BALB C , Humans , Particle Size , Thiophenes/chemistry , Thiophenes/pharmacology , Surface Properties , Photochemotherapy , Nanoparticles/chemistry , Phototherapy/methods , Cell Line, Tumor , Female , Cell Proliferation/drug effects , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Cell Survival/drug effects , Porosity
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